In order to investigate the genetic control of human immune responses, the inheritance of several genes known to play important roles in a variety of immune processes has been analyzed in human families. HLA and T cell receptor (TCR) genes have been examined by Southern blot analyses using specific DNA probes. A total of six restriction fragment length polymorphisms (RFLP) associated with the TCR alpha gene complex were identified including three for the C region and three for V gene segments. In addition to one polymorphism associated with the TCR beta C region gene segments, seven TCR beta V RFLP detected with four different probes were examined. The results of these studies confirm the expected linkage of V and C gene segments for both TCR alpha and beta gene complexes. Polymorphism detected in genomic DNA samples with any given probe and restriction enzyme combination was limited. In most cases, two polymorphic fragments that segregated as alleles were observed. No evidence for deletion or expansion of a V gene family was obtained. Differences in the number of fragments hybridizing with a given probe could be attributed to homozygosity or heterozygosity for observed polymorphisms. Examination of the combination of markers present in a haplotype revealed extensive heterogeneity at this level for both TCR alpha and beta chain genes, 14 different combinations of the six TCR alpha markers and 12 combinations of the eight TCR beta markers were observed in the 32 parental haplotypes examined. The observation that a series of markers each displaying few allelic forms are present in multiple combinations suggests that recombination has occurred frequently in both TCR alpha and beta chain genes. Identification of individuals who inherited recombinant TCR genes supports this concept. These polymorphisms will provide useful markers that will facilitate linkage studies, mapping studies, genetic analyses of T cell function, and the means of evaluating the role of TCR genes in disease susceptibility.